Weimer Micro Lab

Contributed by Azarene Foutouhi

Many site-specific micro biomes of the Human body have been well established and studied in an effort to develop micro biome targeted diagnostics and individualized medicine. In general, these communities reach maturation around 2-4 years of life, and recent studies have found that changes a child’s oral microbiome, more specifically its maturity, are predictive of oral disease well in advance of the appearance of dental caries.

Dental caries are the most common form of oral disease in children, and puts and individual at a significantly higher risk for developing caries as an adult. While previously it has been difficult to predict cavities in healthy children, a study which tracked the development of the oral microbiomes over the course of 2 years of 50 children with similar meal plans and oral hygiene found that children with less mature oral microbiomes had more severe dental caries. Parallel effects have been found in studies of the maturation of the gut microbiome, in which malnutrition has been associated with a less developed microbiome.

By looking at certain groups of microbes within the oral microbiome, researchers developed a model that could predict which child will develop dental caries with over 80% accuracy. The importance of the microbiome in diagnostic medicine is especially clear in this case, as an idividual’s oral microbiome could alert a dentist to disease before any outward signs become apparent, when preventative measures are still available.

http://www.the-scientist.com/?articles.view/articleNo/43952/title/Telltale-Mouth-Microbes/

Submitted by Narine Arabyan

Salmonella enterica spp. enterica sv Typhimurium is one of the most important foodborne pathogens causing gastroenteritis in humans¹. WHO (2005) with USDA and CDC estimated that Salmonella infections account for 1.4 -1.6 million cases per year of foodborne illnesses in USA and approach 1.5 billion cases worldwide². Salmonella infections result in about 5000 deaths making it one of the most common enteric pathogens³. The economic impact of Salmonella infections on human health in the United States is estimated to cost up to $2.3 billion dollars per year. The occurrence of this bacterium continues to persist in causing disease in humans, largely via the food supply, indicating that additional effort is needed to define new interventions. This combined with emergence of hypervirulent isolates suggest that the genetic diversity is effectively circumventing the control strategies for this organism². Increased surveillance, current approaches of biocontrol, additional hygiene intervention, and animal vaccinations are not effective in controlling Salmonella in the food supply. As an invasive pathogen, Salmonella needs to gain access to the host cell membrane before entering the intestinal cell. Epithelial cells in the gastrointestinal tract are covered with multiple layers of complex oligosaccharides (mucin and glycocalyx) that protect the cell from the local environment and infection⁴. The glycocalyx layer, composed of diverse glycans, is a complex barrier that is a component of lipid rafts, and are attached to transmembrane glycoproteins and glycolipids used by bacteria as receptors, to mediate infection^5,6. Use of the glycan by viruses, such as avian influenza is well recognized, especially via sialic acid^7-9. Recently, our group discovered that Salmonella degrades the cellular glycan via sialic acid during infection opening many new questions about what specific glycosyl hydrolases (GHs) are used to degrade the glycans to invade the host cell¹⁰. Specific genes in the microbe are needed to degrade the glycan during infection. These genes are poorly characterized and ill-defined. We defined that Salmonella Typhimurium contains 48 annotated genes for GHs that may degrade the glycan and promote infection. Weimer’s group (Arabyan et al. 2016) demonstrated that Salmonella degrades the glycan using GH enzymes to reach the membrane and change infection¹⁰. This innovative approach along with innovative set of genes has opened a novel avenue in defining glycan degrading genes as new targets for controlling infection and persistence in Salmonella and other enteric pathogens.

This recently published paper can be found at http://www.nature.com/articles/srep29525.

1. Thiennimitr, P., Winter, S. E. & Baumler, A. J. Salmonella, the host and its microbiota. Current opinion in microbiology 15, 108-114, doi:10.1016/j.mib.2011.10.002 (2012).
2. Heithoff, D. M. et al. Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature. PLoS pathogens 8, e1002647, doi:10.1371/journal.ppat.1002647 (2012).
3. Scallan, E. et al. Foodborne illness acquired in the United States–major pathogens. Emerging infectious diseases 17, 7-15, doi:10.3201/eid1701.091101p1 (2011).
4. Moran, A. P., Gupta, A. & Joshi, L. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60, 1412-1425, doi:10.1136/gut.2010.212704 (2011).
5. McGuckin, M. A., Linden, S. K., Sutton, P. & Florin, T. H. Mucin dynamics and enteric pathogens. Nature reviews. Microbiology 9, 265-278, doi:10.1038/nrmicro2538 (2011).
6. Varki, A. Evolutionary forces shaping the Golgi glycosylation machinery: why cell surface glycans are universal to living cells. Cold Spring Harbor perspectives in biology 3, doi:10.1101/cshperspect.a005462 (2011).
7. Walther, T. et al. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS pathogens 9, e1003223, doi:10.1371/journal.ppat.1003223 (2013).
8. Chan, R. W. et al. Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis. Influenza and other respiratory viruses 7, 1269-1282, doi:10.1111/irv.12144 (2013).
9. de Graaf, M. & Fouchier, R. A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. The EMBO journal 33, 823-841, doi:10.1002/embj.201387442 (2014).
10. Arabyan, N. et al. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6, 29525, doi:10.1038/srep29525 (2016).

Contributed by Poyin Chen

Nowadays you can’t go two months without hearing about a food recall for Listeria or Salmonella contamination. Luckily with our advances in pathogen detection and tracking, we are able to identify and prevent outbreaks before they occur. But what happens when a bacterial pathogen is able to slip by our first line of defense undetected?

Before a foodborne pathogen can establish an infection in the gut, it must first be able to recognize and bind to the appropriate host cell receptors. This requirement is what allows us to set up our second line of defense using prebiotics. Prebiotics come in many forms and include lipids such as fish oil, and oligosaccharides, such as mannanoligosaccharides (MOS) and human milk oligosaccharides (HMO). These prebiotic oligosaccharides are non-digestible to the host and are thought to work either by providing decoy receptor binding sites for pathogens, or by interacting with host cells to alter the host receptors such that pathogens are no longer able to bind as efficiently (Figure 1).

In vitro studies on the effects of MOS and HMO host treatment prior to bacterial infection indicate that these oligosaccharides may be useful in decreasing pathogen association although the mechanism of protection is unknown. As part of my dissertation studies, I am using a multi-omics approach and enrichment analyses to determine the different gene expression and metabolic pathways that are induced during treatment with MOS versus with HMO. Stay tuned for results!

Figure 1

Contributed by Alli Weis

The Olympics are upon us in Rio de Janeiro, Brazil, and with the merriment and competition comes serious warnings of the Zika Virus. Zika is transmitted by the mosquito in endemic areas and; additionally, has recently been shown to be a sexually transmitted disease. Brazil is a hotspot for viral transmission, and athletes are being cautioned to stay away from mosquito-infested areas, wear repellent (particularly with deet) use mosquito netting, and do not have unprotected sex. The World Health Organization (WHO) has now designated the virus a public health emergency of international concern and has estimated that up to 4 million people could become infected by the end of the year 2016. Almost 60 countries (as of May, 2016… possibly more now) have reported a Zika Virus outbreak.

Zika has spread to the United States. In recent reports from the CDC and reported by the NY Times, Wynwood, a neighborhood in Miami, Florida is ground zero for Zika in the US. Research has progressed on Zika and the link between the virus and microencephaly has been strengthened. Pregnant women are most affected by the virus (along with their fetus) and the virus seems to be causing the drastic effects of small-headedness, mental retardation and abnormalities. In addition to those severe symptoms, the average non-pregnant person will experience a fever, rash, and/ or joint pain. While the spread of the disease is alarming, most people have been reported as not being in a panic about it. It’s bad, but it’s not something we’ll die from seems to be the sentiment.

Here are some references:

http://www.cdc.gov/zika/intheus/florida-update.html

http://www.nytimes.com/2016/08/09/health/zika-virus-florida.html?_r=0

http://internationalmedicalcorps.org/zikaresponse?gclid=CM_aoJy8tc4CFQxufgodmwUMzw

Contributed by Carol Huang

On July 29, 2016, SM Fish Corp. of Far Rockaway, NY, is voluntarily recalling OSSIE’S brand ready-to-eat Herring Salads for its potential of contaminated with Listeria monocytogenes. Listeria was found in multiple locations throughout the facility by the FDA sampling and inspectional findings. Fish Corp. has ceased production and distribution of products following discussion with FDA on July 27. No illness reported to this date.

July 28, 2016, ConAgra Foods is voluntarily recalling additional package codes of Watts Brothers Farms Organic Mixed Vegetables, Organic Super Sweet Corn (Yellow/Gold), and Organic Peas due to the potential for to be contaminated with Listeria monocytogenes, which were first recalled on May 5, 2016. The products covered by this recall were distributed in the U.S. and sold at Costco. There have been no confirmed illnesses to date from the products listed for recall.

On April 22, 2016, CRF Frozen Foods recalled 11 frozen vegetable products because they may be contaminated with Listeria. On May 2, 2016, CRF Frozen Foods expanded its recall to include all frozen organic and traditional fruit and vegetable products manufactured or processed in CRF Frozen Foods’ Pasco facility since May 1, 2014. These products have “best by” dates of April 26, 2016, through April 26, 2018, and may have been purchased in all fifty U.S. states and the following Canadian Provinces: British Columbia, Alberta, Manitoba, and Saskatchewan,

July 15, 2016, FDA Investigated Listeria Outbreak Linked to Frozen Vegetables.

Listeria is an organism which can cause serious and sometimes fatal infections in young children, frail or elderly people, and immunocompromised persons. Healthy individuals may suffer only short-term symptoms such as high fever, severe headache, stiffness, nausea, abdominal pain and diarrhea, Listeria infection can cause miscarriages and stillbirths among pregnant women.

According to CDC, about 1,600 people in the US get sick from Listeria germs each year; Listeria is the 3rd leading cause of death from food poisoning. Nearly all cases in persons who are not infants result from eating food contaminated with L. monocytogenes;

Listeria is a hardy germ that is hard to control. The challenges are the sickness may not occur until weeks later when it is difficult to identify which food was the source, it can even grow on foods that are refrigerated.

Quick identify the infection sources is critical. Whole genome sequencing on clinical, food, and environmental L. monocytogenes isolates provides high-resolution genetic information to aid the investigation of outbreaks by decreasing the time from outbreak detection to public health intervention.

Contributed by Nguyet Kong

Escherichia coli (E. coli) is a bacterium that is naturally found in healthy humans and animals gut, but there is some E. coli that are bad and cause disease. E. coli O157 is a common type of infection that cause people to get sick due to the Shiga-toxin that the bacteria produced. Symptoms can range from diarrhea, fever, cramps and vomiting with the illness ranging from mild to severe. Young children can die from E. coli infections. Animals that spread E. coli to humans include cows and other farm animals. Most people become infected with E. coli through contaminated food such as undercooked meat or unpasteurized milk, so E. coli can pass to people.

In a recent study from Michigan State University found that cow under stress from hot weather and energy loss from milk production was more likely to shed Shiga toxin producing E. coli (STEC), which is a type of E. coli that cause serious sickness in humans. This finding provide an opportunity for prevention practices to reduce the spread of E. coli, which cause ~100,000 illness, 3000 hospitalizations and 90 deaths yearly in the United States. This study involved 6 cattle farmers with over 1000 cattle in the Michigan area, it helps bring awareness to improve the safety and quality of the food that is being produced.

Venegas-Vargas C, Henderson S, Khare A, Mosci RE, Lehnert JD, Singh P, Ouellette L, Norby B, Funk JA, Rust S, Bartlett P, Grooms D, Manning SD. 2016. Factors associated with Shiga toxin-producing Escherichia coli shedding in dairy and beef cattle. Appl Environ Microbiol. 2016 Jun 24. pii: AEM.00829-16

http://www.fsis.usda.gov/wps/portal/fsis/topics/food-safety-education/get-answers/food-safety-fact-sheets/foodborne-illness-and-disease/escherichia-coli-o157h7/CT_Index

http://www.cdc.gov/ecoli/

http://www.mayoclinic.org/diseases-conditions/e-coli/basics/causes/con-20032105

http://www.about-ecoli.com/ecoli_transmission/#.V4zxAzWNH7M

Contributed by Azarene Foutouhi 

Earlier this month, General Mills voluntarily recalled a newly expanded list of flour products including Gold Medal Flour, Signature Kitchens Flour, and Gold Medal Wondra Flour after Shiga Toxin producing Escherichia coli 0121 was isolated from product samples taken from the homes of ill consumers. Thus far, the contaminated product has been linked to illness in 21 states, with Eighty-one percent of those afflicted being female, with a median age of 18. Consumers have been advised to thoroughly cook items containing flour, and to refrain from eating raw dough or batter.

While many serotypes of E. coli do not cause disease state in animals, Escherichia coli 0121, like Escherichia coli 0157 produces Shiga Toxin, which acts to inhibit protein synthesis in a mechanism similar to that of Ricin. Shiga Toxin is associated with Hemolytic Uremia Syndrome (HUS), and renal failure, both of which have no therapy and are potentially fatal. First identified in 1955, HUS has since been understood as the most common cause of acute kidney failure in young children.

Shockingly, usage of antimicrobials during the diarrheal phase of illness caused by E. coli 0121 has been shown to have a harmful effect by inducing Shiga Toxin production. As the offending bacteria rapidly multiply within the gut, they bind closely to the cells of the large intestine, and the tight proximity allows the Shiga Toxin to be absorbed and eventually encounter its receptors. Soon follows a rapid succession of cell death, clots, kidney failure, and damage to the spleen.

Some animals such as cattle and pigs entirely lack Shiga Toxin receptors, thereby resulting in food animals that constantly shed Shiga Toxin producing E. coli.

Thorpe, C. M. “Shiga Toxin–Producing Escherichia Coli Infection.” Clinical Infectious Diseases 38.9 (2004): 1298-303. Web.  http://www.about-hus.com/

Narine Arabyan, Poyin Chen, Allison Weis, Dr. Bart Weimer

Contributed by Bart C. Weimer, PhD

It is spring and again graduation is upon us. This year the Weimer lab produced 4 fantastic graduates. These folks are prepared for the next phase of their career. Moving from being a graduate student to a post doc or an industry employee is a big transition. Prior to the ceremony a friend of one of my students came by to wish all a great day. She said, “Industry is so demanding and deadline driven. I’m having troubles keeping up with the deadlines.” What a real world comment. Graduate school is a privileged part of life where you have lots of flexibility to think, write and do science while disregarding the demands for progress on a quarterly schedule. While I try to honor this privilege, my long years of collaborating with industry tells me that I need to instill a sense of timing for my graduate students so this transition is smoother.

All of my students that are graduating (Narine, Po, Alli, Ning) have very different projects. They have done a stunning job of working on very hard problems to discern fundamental insights so that translational insights will also be found. I’m really sorry to see these students leave, but that is my job – train people to move on and get on with their career so that they are a great success with a solid foundation.

Each of these students has been exceptional in very different ways. It has been a pleasure to work with them and interact to produce science that has substance and that we can be proud of now and in the future. They will be at ASM to show off their great science. Please stop and see their posters in Boston on June 18!! You will see glycan digestion from pathogens, metabolomic assessment of infection, large scale genomics of Campylobacter and hazard forensics using metagenomics – all have great data for their posters, and papers that are in progress.

Best of luck to my departing students. I will miss them. They have added and enriched my lab with their work and personalities. I’m sure they will succeed. It is part of their DNA to push, drive, and produce great science.

Join us for a Special Symposium
ASM Microbe 2016 – BOSTON

Industrial Metagenomics – Large Scale Analysis for Food Safety

June 18th, 2016 6:45pm – 10:00 pm 
Boston Convention Center Grand Ballroom West

The program will highlight the microbial ecology of foods as they relate to food safety and microbial diversity in the micro biome. Speakers will discuss technical aspects of defining the microbiome using metRNAseq to determine microbe ID, function, and forensic assessment of hazards in the food supply.

Mapping microbiome data to predict food safety risks
Jose Clemente PhD; Dept. of Genomics & Multiscale Biology, Icahn School of Medicine at Mt. Sinai

Metagenomics in the beef processing chain
Noelle Noyes, PhD; Dept. of Clinical Sciences, Colorado State University

A new method for rapid, culture-free whole genome assembly from mixed microbial communities

Ivan Liachko, PhD; Dept. of Genome Sciences, University of Washington

Mapping the Metagenome with an Ever Smaller Ruler
James Kaufman, PhD; Manager, Public Health Research, IBM Research, Almaden Research Center

Using metaRNAseq in the food chain for microbial hazards
Bart Weimer, PhD; Dept. of Population Health and Reproduction, School of Veterinary Medicine, UC Davis

MODERATORS:
Christopher Elkins, PhD; Director, Division of Molecular Biology, FDA/CFSAN
Kristen Beck, PhD; Researcher, IBM Research, Almaden Research Center
David Chambliss, PhD; Principal Researcher, IBM Research, Almaden Research Center

Industrial Metagenomics – Large Scale Analysis for Food Safety
Supported by UC Davis, IBM, Mars, Inc. and Bio-Rad
6:45 pm – 10:00 pm
Boston Convention and Exhibition Center,
Grand Ballroom West

MODERATORS:
Christopher Elkins PhD; Supervisory Microbiologist, FDA
Kristen Beck, PhD; Researcher, Sequencing the Food Supply Chain, IBM Research, Almaden Research Center

PRESENTATIONS:

Mapping microbiome data to predict food safety risks
Jose Clemente PhD; Department of Genomics & Multiscale Biology, Icahn School of Medicine at Mt. Sinai, New York, NY

A new method for rapid, culture-free whole genome assembly from mixed microbial communities
Ivan Liachko, PhD; Department of Genome Sciences, University of Washington, Seattle, WA

Metagenomics in the beef processing chain
Noelle Noyes, PhD; Department of Clinical Sciences, Colorado State University, Fort Collins, CO

Using metaRNAseq in the food chain for microbial hazards
Bart Weimer, PhD; School of Veterinary Medicine, Department of Population Health and Reproduction, University of California – Davis, Davis, CA

From Metagenomics to Epidemiology, the molecular diversity of life
James Kaufman, PhD; Manager, Public Health Research, IBM Research, Almaden Research Center, San Jose, CA

Overview: The program will highlight the microbial ecology of foods as they relate to food safety and microbial diversity in the micro biome.  Speakers will discuss technical aspects of defining the microbiome using metRNAseq to determine microbe ID, function, and forensic assessment of hazards in the food supply.